Pancreatic islet structure and function in JCR:LA-corpulent rats

Karim Louchami, Charles Nicaise, Nurdan Bulur, Emeline Hupkens, Willy J Malaisse, Abdullah Sener

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Abstract

JCR-LA-corpulent rats, homozygote for the cp gene, represent a current animal model for obesity and hyperlipemia. The
present study refers mainly to secretory and histological findings made in the islets of these rats. Male fed Wistar rats and both
lean and obese LA/N rats were killed under CO2 anesthesia. Histological data were obtained in pancreatic sections. Pancreatic
islets were isolated by the collagenase procedure. Despite a higher age, the lean LA/N rats displayed lower body weight and
epididymal fat weight than control Wistar rats. Their plasma glucose and insulin concentrations, plasma insulin/glucose ratio,
HOMA for insulin resistance, islet mean size (μm²) and basal insulin output by islets exposed to 2.8 mM glucose did not differ
significantly from those recorded in the control Wistar rats. Over 90 min incubation at 16.7 mM glucose, however, the release of
insulin was 28.7 % higher (p < 0.005) from the islets of lean LA/N rats as compared to Wistar rats, despite a lower islet protein
and insulin content (p < 0.05) in the former than latter animals. When compared to lean LA/N rats of similar age, the obese
LA/N rats displayed higher body weight, 5-fold higher epididymal fat weight, and abnormally high plasma glucose and insulin
concentrations, plasma insulin/glucose ratio and insulin times glucose product. The number of islets per mm² was twice higher,
their mean size 5 times higher, and the basal insulin output twice higher in obese, as compared to lean, LA/N rats. At 16.7 mM
glucose, the insulin output/content ratio was also twice higher in obese compared to lean LA/N rats. The immunohistochemical
staining of the islets for GLUT2 yielded a patchy distribution in the islets of obese LA/N rats as distinct from a homogenously
dense pattern in the islets of either lean LA/N rats or Wistar rats. The present results indicate that the total islet volume is about
22 times higher in obese than in lean LA/N rats, the former rats being eventually considered as suitable for non-invasive
imaging and quantification of pancreatic insulin-producing cells in an animal model with severely increased ß-cell mass.
Original languageEnglish
Pages (from-to)9-14
Number of pages6
JournalMetabolic and Functional Research on Diabetes
Publication statusPublished - 2010

Keywords

  • JCR:LA-cp rats
  • insulin resistance
  • hyperinsulinism
  • isolated pancreatic islets
  • insulin secretion
  • pancreatic ßcell mass

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